Project Summary Imaging of biological specimens must be performed with high spatial and temporal resolution, while at the same time avoiding damage to the sample. Present techniques, such as optical microscopy and transmission electron microscopy (TEM), are valuable and widely-used tools in biomedical studies/research, but have limitations. For example, the resolution of optical microscopy is not as high as that which can be obtained using short-wavelength light. For TEM, sample preparation is tedious and risks altering the sample structure. A microscope operating in the water-window wavelength region (= 2.3 - 4.4 nm) provides high resolution as well as a large depth of focus, which enables performing micro-tomography. Microscopy at this wavelength provides a strong natural contrast between water and carbon-rich tissues such as proteins and lipids. Very recently water-window microscopes using synchrotron radiation showed great potential for high resolution three-dimensional tomographic images of frozen cells. However, the limited accessibility and large expense associated with synchrotron-based sources significantly limits the role of WW microscopy in biomedical research. The full potential of WW microscopy will only be realized if it becomes widely accessible to a broad variety of medical laboratories and research facilities. In this project, we propose to develop an efficient, table-top water-window radiation source for transmission X-ray microscope (TXM) based on laser- produced plasma (LPP) light source. LPP-based WW-TXM systems require a soft X-ray source that is efficient, stable and debris free. LPP sources are viable light sources for WW-TXM, but up to now have been limited by their relatively low poor efficiency in converting laser energy into useable soft X-ray light. Low efficiency of LPP sources leads to longer exposure time for imaging of a biological sample. It implies efficient or high conversion efficiency (CE, conversion from laser energy to WW radiation) LPP sources are prerequisite for using them as a source for WWW-TXM. CE of a LPP depends on numerous laser and target characteristics and it is very challenging to identify optimum parameters for obtaining optimum CE. This can be attained only through a combination of modeling and experimental work. We will use our state-of-the-art radiation and atomic physics simulation tools to identify laser and source characteristics that produce highly efficient soft X- ray sources, and guide the experimental campaign for developing novel light sources. This project will lead to affordable, table-top soft X-ray light source in the water-window region that will be of significant benefit to the fields of biomedical research and cell biology. PUBLIC HEALTH RELEVANCE (provided by applicant): Project Narrative Images of biological cells are fundamental in many areas of medical and biological research. We propose to develop an efficient table-top light source instrument for water-window Transmission X-ray microscope (WW-TXM). Compact WW-TXM can provide highly detailed, high contrast images of carbon based structures in biological cells, while minimizing the impact of the water based growing medium, will ensure that this exciting technique is readily available to the maximum number of researchers.